The promise of viral therapies

At any other moment in Brad Thompson's life it might have sounded too strange.

But when University of Calgary researchers approached the entrepreneur in 1998 about the potential of using a common stomach bug to fight cancer, their timing was uncanny.

Dr. Thompson had lost his mother to lung cancer that year, his uncle to esophageal cancer and he himself had been diagnosed with melanoma.

"I was open to thinking about cancer, and thinking about it in a new way," said the microbiologist, who was working with a biotech firm on bowel diseases at the time.

Doctors David Stojdl, left, Harry Atkins and John Bell, pictured at the Ottawa Regional Cancer Centre this week, are among the scientists working in the field of viral cancer therapy. (Bill Grimshaw for The Globe and Mail)

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Eight years later, Dr. Thompson, now CEO of Calgary-based Oncolytics Biotech, is in the vanguard of one of the more promising, if unconventional, approaches to treating cancer patients: deliberately infecting them with viruses.

Cancer cells, it so happens, are particularly vulnerable to viral invasion and the century-old concept has cured laboratory mice, pushed some end-stage cancer patients into long-term remission and raised hopes for a new generation of cancer therapies.

Hundreds of patients in clinical trials in Canada, the United States and Europe have volunteered to catch a cold, a stomach bug, a mutant form of herpes and even a chicken flu.

Researchers have found cancer cells lack the defences that healthy cells have to protect themselves from infection. Flipped into overdrive, a cancer cell never shuts down the pathway that allows a viral intruder to waltz in, replicate and wreak havoc.

Several viruses have now passed Phase 1 human safety tests with encouraging results and larger Phase 2 trials to test their efficacy are in the works.

But getting a new medicine to market is never easy and those involved say that transforming a virus into a viable drug presents more obstacles than usual. For one, it can be tricky to control a dose when the drug has the power to replicate itself.

"This is a much more complicated kind of drug, if you can even call it a drug," said David Stojdl, a scientist working at the Ottawa Regional Cancer Centre in the field.

As well, despite years of university research, the field still labours to alter its fringe image. Some academic scientists are struggling to attract the interest of drug companies with pockets deep enough to continue development. Not everyone has been as receptive as Dr. Thompson to the idea of using one disease to fight another.

"Industry is much more conservative, and for them this can be too much," said John Bell, an Ottawa scientist and long-time pioneer in the field.

But the need for private-sector investment is critical, he said: "You can treat mice with government funding, not people."

Earlier this year, China became the first country to approve a viral therapy, giving the nod to a modified version of the common cold to treat cancers of the head and neck. Yet the cold bug now being sold by a Shanghai biotech firm is a copycat of a virus first developed by a U.S. company, which despite encouraging results from mid-stage clinical trials, dropped it in favour of a more conventional drug.

Yet most experts feel it's time to look beyond convention.

"As an industry, we haven't been very successful in new approaches to treating to cancer," Dr. Thompson said. "Most of the advances have been the result of better diagnosis . . . survival times have improved with earlier detection."

He, for example, credits his own quick melanoma diagnosis to his beloved dog, Mozart, who sniffed so steadily at the malignant mole on his leg that he rushed to the doctor to have it checked.

Dr. Thompson knows from experience that "the therapies we use to treat cancer are still the same ones we've had for years.

"Viral therapies are promising, they're safe, they target the cancer cells and there's not much collateral damage."

It began as one of those weird medical observations. An Italian doctor in the early 1900s noticed that after he gave a prostitute a rabies vaccine to treat a dog bite -- a shot that contains viral material -- her cervical cancer regressed.

The mysterious connection -- bolstered by anecdotes about cancer patients getting better when they battled a cold, flu or other infection -- led to a few experiments. Reports from the 1940s suggested that measles might somehow help to quell lymphoma. In the 1950s, doctors in the Soviet Union literally fed poliovirus to cancer patients.

But not until the early 1990s did virologist Patrick Lee and colleagues at the University of Calgary piece the puzzle together.

They showed that in a cancer cell, a pathway crucial for growth and survival is stuck in the "on" position. Like a porch light that never shuts off, this defective mechanism that makes a cell malignant also allows a virus to find the door easily.

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